The model of rat cortical tissue maintained in dissociated cell culture, which is characterized by long neuronal survival time (6-12 weeks), regular formation of excitatory and inhibitory synapses, high level of GABA sensitivity in almost all neurons and controllable numbers of non-neuronal cells will be expanded into a multidimensional interdisciplinary system by biochemical and pharmacological studies of transmitter function. We shall focus upon: 1. What agent(s) is the inhibitory transmitter? Preliminary evidence suggests that it is GABA in this system. 2. What determines the number and properties of synaptic receptors in the cerebral cortex? What other factors contribute to the sensitivity of cortical neurons to transmitters. 3. What is the effect of chronic treatment with drugs which act on specific transmitter functions, on synapses and synaptic function? How can we modify GABA synapses to increase or decrease synaptic inhibition? 4. What are the effects of treatment with other CNS-active drugs (for example, anti-convulsants and neuroleptics) on synaptic function and on synaptogenesis? 5. What effect does synapse formation have upon membrane properties, receptor density and cellular regulation? 6. Can we prevent synapse formation without killing neurons? What would this tell us about the mechanisms of synapse formation?